Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Amelia J. Eisch, John F. Marshall

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro- Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 ± 0.10°C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4°C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37°C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m- AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m- AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.

Original languageEnglish (US)
Pages (from-to)433-445
Number of pages13
JournalSynapse
Volume30
Issue number4
DOIs
StatePublished - Dec 1998

Keywords

  • Accumbens
  • Fluoro-Jade
  • GBR- 12909
  • Somatosensory cortex
  • Stimulant
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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